Increased Serum Triglyceride Research Articles

Inhibition of acetyl-CoA carboxylase by PP-7a exerts beneficial effects on metabolic dysregulation in a mouse model of diet-induced obesity.

Acetyl-coenzyme A carboxylase (ACC) is a critical regulator of fatty acid metabolism and represents a promising therapeutic target for metabolic diseases, including obesity, type 2 diabetes and non-alcoholic fatty liver disease. Recently, a novel ACC inhibitor, PP-7a, was developed by our group by utilizing a structure-based drug design. In the present study, the pharmacological effects of PP-7a on the metabolic dysregulation in mice with high-fat diet (HFD)-induced obesity and the underlying mechanisms were investigated. The inhibitory effect on ACC activities was confirmed by assessing the level of malonyl-CoA, a product synthesized by the catalyzation of ACC. Following 16 weeks of being fed an HFD, the mice were administered PP-7a (15, 45 or 75 mg/kg) for 4 weeks. The effects of PP-7a on weight gain, glucose intolerance, hepatic lipid accumulation and the increase of serum triglyceride (TG), total cholesterol (TC) and free fatty acids (FFA) in mice were assessed. CP-640186 was used as a positive control drug and administered in the same manner as PP-7a. Chronic administration of PP-7a lowered the malonyl-CoA levels in liver and heart tissues of mice in the HFD group. In addition, HFD-induced weight gain and glucose intolerance were improved by PP-7a treatment in the mice fed the HFD. Furthermore, PP-7a suppressed hepatic lipid accumulation and the increase in TG, TC and FFA levels. Taken together, these results suggest that ACC inhibition by PP-7a may have a beneficial effect on metabolic dysregulation in obese mice.

Interactive effect of high sodium intake with increased serum triglycerides on hypertension.

BackgroundA high salt diet is associated with the development of hypertension, one of the most important cardiovascular risk factors. A reduction in sodium intake seems to have an effect on increasing serum triglycerides (TGs). Elevated TGs are independently linked to cardiovascular risk. However, there is limited evidence of a possible interactive effect of sodium intake and serum TGs on high blood pressure (BP).MethodsWe conducted a nationwide, population-based interaction analysis using the Kawasaki method for estimating 24-h urinary sodium excretion (e24hUNaEKawasaki) as a candidate indicator of dietary sodium intake. All native Koreans aged 20 years or older without significant medical illness were eligible for inclusion.ResultsA total of 16936 participants were divided into quintiles according to their e24hUNaEKawasaki results. Participants in the highest quintile were more obese and hypertensive and had higher white blood cell count, lower hemoglobin, greater glycemic exposure, and poor lipid profiles compared to the same parameters of individuals in other quintiles. Linear regression revealed that e24UNaEKawasaki was related to systolic BP, diastolic BP, and TGs. Multiple logistic regression, adjusted for dietary sodium intake and various conventional risk factors for chronic vascular diseases, showed that both e24UNaEKawasaki and TGs were significant predictors of hypertension. Our interaction analysis demonstrated that increased sodium intake was associated with higher risk of hypertension in participants with elevated TGs than in those without (adjusted RERI = 0.022, 95% CI = 0.017–0.027; adjusted AP = 0.017, 95% CI = 0.006–0.028; adjusted SI = 1.010, 95% CI = 1.007–1.014).ConclusionOur findings suggest that the interaction between a high salt diet and elevated TGs may exert synergistic biological effects on the risk of hypertension.

Western Diet‐Induced Hypertension involves HMGB1/TLR4 Signaling in Perivascular Adipose Tissue of Female Rats

BackgroundOverconsumption of a Western Diet (WD), a high‐fat and high‐sugar diet, is a major factor implicated in rising obesity rates in the US. Perivascular adipose tissue (PVAT) possesses a vasculo‐protective role. In obesity, PVAT expands and becomes inflamed, contributing to vascular complications. High motility group box 1 (HMGB1), a cytokine, has been demonstrated to mediate vascular inflammation. Recent studies also suggest that PVAT plays a role in obesity‐related hypertension; however, the underlying mechanisms are still not well understood. We hypothesize that WD increases HMGB1 production in PVAT which in turn activates Toll‐like receptor 4 (TLR4) signaling in an autocrine/paracrine manner, resulting in hypertension.MethodsWe have established a model of WD‐induced hypertension in female rats. Adult female Wistar rats (n= 9) were randomized into two groups. Control Group (n= 4) received a regular chow diet (5% fat, 48.7% carbohydrates [3.2% sucrose], and 24.1% protein) and WD group (n= 5) received WD (40% fat, 43% carbohydrates [34% sucrose], and 17% protein) for 28 weeks. Metabolic parameters (body weight, body mass index (BMI), triglycerides, and non‐esterified free fatty acids [NEFA]) were assessed. Arterial blood pressure was measured via carotid catherization at the end of the experimental protocol. Thoracic aortas with PVAT were obtained for vascular studies and molecular assays. Vascular studies were performed using a wire myograph to assess vasodilatory responses.ResultsBody weight (358.9 ± 10.2 vs 270.1 ± 12.3g controls, p<0.005) and BMI (0.68 ± 0.02 vs. 0.06 ± 0.03 g/cm2controls, p<0.005) were increased in the WD group, confirming obesity. The WD group also demonstrated increased serum triglycerides (49.8 ± 4.7 vs. 14.3 ± 1.8mg/dL controls, p<0.05) and NEFA (0.57 ± 0.02 vs. 0.79 ± 0.04 mM controls, p<0.05). WD increased systolic blood pressure (144.04 ± 2.8 vs. 115.1 ± 3.9 mmHg controls, p<0.001), diastolic blood pressure (108.3 ± 3.1 vs. 89.5 ± 4.3 mmHg controls, p<0.01), and heart rate (386.1 ± 8.8 vs. 307.7 ± 40.3 bpm controls, p<0.05). Impaired vasodilation in the WD group in comparison to controls was worsened in the presence of PVAT, suggesting dysfunctional PVAT. Histological analysis of PVAT revealed a switch from brown‐like adipose tissue to white‐like adipose tissue, along with a significant decrease in uncoupling protein 1 (UCP‐1) expression (1.5‐fold decreased, p<0.05), a marker of thermogenesis. An oxidative/inflammatory state in the PVAT was confirmed by a 50% increase in reactive oxygen species levels (p<0.01). Strikingly, the novelty of this study revealed increased HMGB1 expression (2.0‐fold increased, p<0.05) along with increased TLR4 expression (2.5‐fold increased, p<0.05) in the PVAT of the WD group.ConclusionOur findings suggest that upregulated HMGB1/TLR4 signaling in the PVAT may induce a local inflammatory response through an autocrine/paracrine manner in the vasculature, contributing to dysregulation of blood pressure in the context of obesity.Support or Funding InformationNIH

Evidence for Associations Between Th1/Th17 "Hybrid" Phenotype and Altered Lipometabolism in Very Severe Graves Orbitopathy.

The purpose of this article is to investigate the characteristics of Th1-cell and Th17-cell lineages for very severe Graves orbitopathy (GO) development. Flow cytometry was performed with blood samples from GO and Graves disease (GD) patients and healthy controls, to explore effector T-cell phenotypes. Lipidomics was conducted with serum from very severe GO patients before and after glucocorticoid (GC) therapy. Immunohistochemistry and Western blotting were used to examine orbital-infiltrating Th17 cells or in vitro models of Th17 polarization. In GD, Th1 cells predominated in peripheral effector T-cell subsets, whereas in GO, Th17-cell lineage predominated. In moderate-to-severe GO, Th17.1 cells expressed retinoic acid receptor-related orphan receptor-γt (RORγt) independently and produced interleukin-17A (IL-17A), whereas in very severe GO, Th17.1 cells co-expressed RORγt and Tbet and produced interferon-γ (IFN-γ). Increased IFN-γ-producing Th17.1 cells positively correlated with GO activity and were associated with the development of very severe GO. Additionally, GC therapy inhibited both Th1-cell and Th17-cell lineages and modulated a lipid panel consisting of 79 serum metabolites. However, in GC-resistant, very severe GO, IFN-γ-producing Th17.1 cells remained at a high level, correlating with increased serum triglycerides. Further, retro-orbital tissues from GC-resistant, very severe GO were shown to be infiltrated by CXCR3+ Th17 cells expressing Tbet and STAT4 and rich in triglycerides that promoted Th1 phenotype in Th17 cells in vitro. Our findings address the importance of Th17.1 cells in GO pathogenesis, possibly promoting our understanding of the association between Th17-cell plasticity and disease severity of GO.

Lipid Profile Pattern in Type 2 Diabetes Mellitus Patients

Introduction: Dyslipidemia has been noted to play an integral role in the pathogenesis and progression of micro and macrovascular complications in Diabetes Mellitus (DM) patients. Lipid profile is the indicators of dyslipidemia.
 Objectives: To evaluate the prevalence and pattern of dyslipidemia in type 2 DM patients.
 Materials and Methods: This cross sectional study was conducted at Armed Forces Institute of Pathology (AFIP) from November 2014 to October 2015. The study included 300 type 2 diabetic patients belonging to the age group 30-59 years. Personal data and history of co-existing medical conditions were collected by data collection sheet and analyzed.
 Results: Among 300 study subjects with type 2 DM the prevalence of dyslipidemia was 94% among them 19% had single dyslipidemia and 75% had multiple dyslipidemia. In this study, high level of total cholesterol (TC), triglycerides(TG) and Low Density Lipoprotein-Cholesterol (LDL-C) were found in 47.3%, 76.7% and 41.3% patients respectively. High Density Lipoprotein- Cholesterol (HDL-C) levels were found to be low in 60% patients.
 Conclusion: The study revealed that dyslipidemia is very common in type 2 diabetic patients and the most common abnormality observed was increased serum TG level followed by decreased HDL-C level. So, patients with type 2 DM should be followed up with serum lipid profile regularly.
 Journal of Armed Forces Medical College Bangladesh Vol.14 (2) 2018: 177-179

Hypertriglyceridemia with total parenteral nutrition versus enteral nutrition in patients with acute pancreatitis

Abstract Background Acute pancreatitis (AP) is an inflammatory condition of the pancreas that can cause local injury, systemic inflammatory response syndrome, and organ failure. Worldwide, AP is a common gastrointestinal condition and there is evidence that the incidence has been rising in recent years. AP is associated with substantial suffering, morbidity, and cost to the health care system. Objective Our study aims to compare between the effect of enteral (EN) and parenteral nutrition on serum triglycerides in patient with acute pancreatitis in intensive care unit of Ain Shams University (ICU). We found that enteral route is more safe than parenteral nutrition regarding serum triglycerides. Patients and Methods An informed written consent was obtained from patients and /or relatives who were included in this study. All patients were adults, more than 18 years old, admitted to ICU of Ain Shams University Hospital, either have acute pancreatitis on admission or acquired acute pancreatitis in ICU due to different causes in period of six months of approval of the protocol. Patients were divided into two groups: 30 patients started total parenteral nutrition TPN ) one day after admission consisting of 70% carbohydrate (in the form of dextrose 25%) and 30% fat (smoflipid 250 ml, 2 gm per ml). The other 30 patients started enteral nutrition rich in carbohydrates with low fat content one day after admission (peptamen) 6 scoops in 200 ml water every 2 hours, stopped from 12 am to 8 am. Serum triglyceride level was measured at first day of admission, then 3 days after admission, then one week after admission. Results Our study showed that TPN was associated with more increase of serum triglycerides level from first day of admission to 3 days after admission when compared with enteral nutrition, there is also increase in serum triglycerides from 3days to one week after admission, comparing the three periods together, there is increase in serum triglycerides with TPN group more than in enteral group. Conclusion The study showed that TPN was associated with higher mortality rate than EN, also there was an increase in serum triglycerides with TPN more than EN; suggesting that, enteral nutrition is a safer mode of nutrition in patients with acute pancreatitis.

Metabolic Response of Adult Male Offspring Rats to Prenatal Caffeine Exposure.

Caffeine is the most widely consumed psychoactive substance, with recommendations from health associations and regulatory bodies for limiting caffeine consumption during pregnancy being increasingly common. Prenatal exposure to caffeine has been shown to increase the risk of developing abnormalities in lipid metabolism in adult life. We further investigated the effect of prenatal caffeine exposure (PCE) (20 mg/kg of body weight) on the metabolic “reserve” of male Sprague Dawley offspring fed on a high fructose diet in adult life. Male adult PCE offspring were assigned to four groups; Nw and Nf: offspring of control mothers (N group of mothers), having received tap water or high fructose water respectively; Cw and Cf: offspring exposed to caffeine during gestation (C group of mothers) and receiving tap water or a high fructose water solution, respectively.Cf rats presented increased serum triglyceride level, as well as raised systolic and diastolic blood pressure levels, together with extensive renal tissue oedema in adulthood, compared to the other groups (p<0.05 for all comparisons). These findings show further evidence for potential detrimental metabolic effects of prenatal caffeine exposure during adulthood in this animal model.

Protein Arginine Methyltransferase 4 Regulates Adipose Tissue Lipolysis in Type 1 Diabetic Mice.

PurposeHypertriglyceridemia is considered to be driven by increased lipolysis in type 1 diabetes mellitus (T1DM). However, information regarding the transcriptional circuitry that governs lipolysis remains incomplete in T1DM. Protein arginine methyltransferase 4 (PRMT4), a transcriptional coactivation factor, promotes autophagy and may play an important role in lipolysis. We wonder whether activated lipolysis in T1DM is regulated by PRMT4.Materials and MethodsRecombinant adeno-associated virus was adopted to overexpress PRMT4 in adipose tissue of mice. Streptozotocin (150 mg/kg) was injected intraperitoneally into mice to induce T1DM. Plasma insulin, triglycerides, free fatty acids (FFAs) levels were determined using commercial assay kits. Differentiated adipocytes were applied to verify the regulation of PRMT4 on lipolysis.ResultsElevated serum triglycerides and FFAs were observed in PRMT4-overexpressed T1DM mice. We also observed that PRMT4 over-expression induced the decrease of fat pads weights and adipocyte sizes. Moreover, expression levels of lipolysis-related molecules, including ATGL, HSL, and MAGL, and HSL phosphorylation levels were increased in PRMT4-overexpressed mice when compared to those of control mice. In vitro, PRMT4 promoted FFAs release and activated HSL phosphorylation, whereas PRMT4 knockdown inhibited these processes.ConclusionPRMT4 promotes lipolysis and increases serum triglyceride in T1DM.

Evaluation of Glucosamine Effect Against Heart and Brain Damage Induced by Y-radiation or Aluminium Chloride in Female Rats

Abstract Glucosamine is known as anti-inflammatory, antioxidant and as neuroprotective as well as using to treat many of diseases. This work aimed to investigate the remedial effect of glucosamine (20mg/kg b.wt) against the damage induced by a single dose of γ-radiation (8Gy) or aluminium chloride (AlCl3) (100mg/kg b.wt) in the heart and brain tissues of female rats. Serum aspartate aminotransferase (AST), cholesterol, triglycerides (TGs), LDH and creatine kinase (CPK) were measured. Moreover, gene expression of amyloid protein precursor (APP) and seladin-1 were estimated in the brain tissue. Also, acetylcholinesterase activity (AChE) and p-tau protein expression were estimated in brain homogenate. Metallothioneine (MT) was estimated in the heart and brain tissues. Heart and brain histopathological examination was performed. Irradiation significantly decreased serum AST, CPK and LDH, as well as MT levels in heart and brain tissues. Also, gene expression of seladin-1 decreased. On the other hand, irradiation significantly increased serum TGs level and brain AchE activity, tau protein, and β-amyloid percursor (APP). AlCl3 administration (21 days) induced disturbance in most of the estimated parameters, especially AST, TGs, and MT. Glucosamine treatment with irradiation or AlCl3 improved most of the measured parameters. In addition, histopathological examination confirmed the biochemical results. In conclusion: Glucosamine could be used to improve the heart and brain damages induced by γ-radiation exposure or AlCl3.

Development of nonalcoholic fatty liver disease model by high-fat diet in rats.

Background Nonalcoholic fatty liver disease (NAFLD) is indicated by liver steatosis without excessive alcohol use or other liver disease. Several studies have reported that metabolic syndromes such as obesity, type 2 diabetes mellitus, and dyslipidemia have a linear correlation associated with NAFLD pathophysiology. One of the characteristics of dyslipidemia in NAFLD is increase in serum triglycerides. This study aimed to develop a model of NAFLD characterized by an increase in serum triglyceride levels and histological profile of liver steatosis by high-fat diet in rats. Methods Twelve Wistar rats were fed with pellets enriched with 60% fat. They were housed individually, and the remaining pellets were weighted every day for intake evaluation. Blood samples were collected at day 0 and at the end of each trial period at days 7, 14, 21, and 28 for the measurement of triglyceride levels. Every animal from each group was also sacrificed for liver histopathological examination. Results This study has established developing the NAFLD animal model by induction of a high-fat diet. The levels of serum triglycerides were increased from baseline 80.41 ± 12.82 to 1152.00 ± 73.62, 493.66 ± 159.98, 556.00 ± 120.79, and 489.00 ± 156.75 mg/dL at days 7, 14, 21, and 28, respectively. Liver histology also showed liver steatosis development, inflammation, and hepatocellular ballooning, which were associated with the NAFLD state. Conclusions High-fat diet in rats induced hypertriglyceridemia along with NAFLD-like liver histopathology.

Changes in nutrient and calorie intake, adipose mass, triglycerides and TNF-α concentrations after non-caloric sweetener intake: A pilot study.

Establishing the safety of non-caloric sweetener consumption in humans is a difficult task, since many contradictory results have been reported. The objective of this study was to compare the effect of frequent intake of sucrose, sucralose or steviol glycosides, on selected anthropometric, biochemical and immunological parameters in healthy, young adults. 38 individuals with normal body mass index were recruited and randomly divided into three experimental groups. After a washout week (where food with added sweeteners was restricted), each group was supplemented with sucrose (8×5g packets/day), sucralose or steviol glycosides (4×1g packets/day each) for 6 weeks. Selected variables were measured before and after treatment in each group and differences within and among groups were assessed. Our results showed that, compared to baseline, there was a modest but significant increase in weight (p=0.0293) in the sucralose group, while the steviol glycosides group reduced their fat mass (p=0.0390). No differences were observed in glycaemia; however, there was a significant increase in serum triglycerides (77.8-110.8mg/dL) and cholesterol (162.0-172.3mg/dL) in the sucrose group, whereas the steviol glycosides group presented lower triglycerides (104.7-92.8mg/dL) and TNF-α concentrations (51.1-47.5pg/mL). Comparison among groups showed differences in serum triglycerides (p=0.0226), TNF-α (p=0.0460) and IL-β (p=0.0008). Our results suggest that, even in a short time span, frequent intake of steviol glycosides may have positive effects on metabolic parameters that may be relevant for human health.

Excessive Fructose Intake Impairs Baroreflex Sensitivity and Led to Elevated Blood Pressure in Rats.

Hypertension development with an increased intake of added sugar, especially excessive fructose intake, was shown in the National Health and Nutrition Examination Survey (NHANES) data. However, the mechanism underlying blood pressure (BP) elevation with increased fructose intake is still unclear. First, the present study showed that in rats fed 10% fructose for one week, BP and fructose/glucose levels increased in the central and peripheral nervous system. Furthermore, increased fructose intake resulted in an upregulation of fructose concentration in the cerebrospinal fluid. Second, consumption of excess fructose increased serum triglycerides. However, the inhibition of triglyceride production did not mitigate sympathetic nerve hyperactivity, but contributed to an insignificant decrease in BP. Finally, increased fructose intake reduced nitric oxide (NO) levels in the nucleus tractus solitarii (NTS) and reduced baroreflex sensitivity within a week. Collectively, the data suggested that fructose intake reduced NO levels in the NTS and caused baroreflex dysfunction, which further stimulated sympathetic nerve activity and induced the development of high BP.

Clofibrate for Non-Hemolytic Icterus in Term Newborns: Randomized-Controlled Trial, Iran

Objectives: To compare the effects of a single dose of clofibrate on the serum bilirubin level in full-term non-hemolytic icteric neonates when it is administered in addition to phototherapy, and to evaluate its possible side effects. Methods: In a randomized-controlled clinical trial in 2016, 90 term icteric neonates were divided into groups of 30. One group took a single dose of 50 mg/kg while another group took a single dose of 100 mg/kg of clofibrate. All neonates were under phototherapy and were compared to a control group who took a placebo. Serum bilirubin levels were measured at admission and then after 6, 12, 24, and 48 hours of treatment. Clofibrate’s side effects were assessed by measuring hepatic enzymes (AST/ALT) and lipid profiles (TG/Chol) at admission and after 48 hours. Results: In neonates with jaundice who were under phototherapy, a single dose of 100 mg/kg of clofibrate decreased the level of serum bilirubin more rapidly compared to the control group (t (58) = -2.73, P = 0.043), or even the group who took a single dose of 50 mg/kg clofibrate (t (58) = -4.261, P = 0.000). A single dose of 50 mg/kg clofibrate did not decrease the serum bilirubin levels more rapidly compared to the control group. Compared to the control group, in the group who took a single dose of 50 mg/kg clofibrate, after 48 hours, a higher number of neonates showed an increase in serum triglyceride (30% versus 63%) and/or cholesterol levels (27% versus 57%). Conclusions: A single dose of 100 (not 50) mg/kg clofibrate better decreased the serum bilirubin.

Potential Biomarkers of Metabolic Syndrome in a Group of Small for Gestational Age Neonates

Objective - Small for gestational age (SGA) infants have an increased risk of developing metabolic syndrome (MS) later in life. The aim of our study was to analyze some of the potential MS biomarkers in SGA neonates and to find the most indicative neonatal biomarker associated with MS in SGA. Materials and Methods - Serum adiponectin, fasting glucose, insulin, total cholesterol, high density lipoprotein (HDL) cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides were evaluated in 43 small (SGA) and 25 appropriate for gestational age (AGA) neonates in the first month of life. Glucose/insulin (G/I) ratio and the homeostasis model assessment of insulin resistance index (HOMA-IR) were calculated. Results - Mean serum adiponectin in SGA was significantly lower than in AGA neonates (36.6 vs. 42.6 mg/L, P=0.021). In SGA infants a statistically insignificant higher fasting insulin levels (9.8 vs. 6.4 mIU/L), lower G/I ratio (1.9 vs. 3.0 mol/IU) and higher HOMA-IR (2.6 vs. 1.4) was observed. The mean serum triglyceride level in SGA neonates was significantly higher than in AGA neonates (1.7 vs. 1.4 mmol/L, P=0.031). Conclusion - SGA neonates demonstrated significantly reduced serum adiponectin and significantly increased serum triglyceride levels in comparison to AGA infants in the first month of life. Triglycerides appeared to be the most promising biomarker reflecting metabolic tendencies in SGA newborns and could possibly be used in predicting the future development of MS.

Antihypertensive and antidiabetic activities of Erythrina senegalensis DC (Fabaceae) stem bark aqueous extract on diabetic hypertensive rats

Erythrina senegalensis is traditionally used in Cameroon for its relaxing and hypoglycemic properties in the treatment of cardiovascular diseases and diabetes. High blood pressure and diabetes mellitus are frequently linked. These pathologies represent major risk factors for cardiovascular and renal diseases. The present study was designed to evaluate the antidiabetic and antihypertensive activity of the stem bark of Erythrina senegalensis aqueous extract in male hypertensive diabetic rats (HDR). Hypertension and diabetes were induced by oral administration of sucrose (15%) and ethanol (40°) at doses of 1.5g/kg and 5g/kg respectively for 30 days, followed by an intravenous injection of streptozotocin (STZ; 40mg/kg). A control group of 5 rats received distilled water (10mL/kg) followed by intravenous injection of 0.9% NaCl (1 mL/100g). HDR were divided into 4 groups of 5 rats each according to their blood glucose level and continued to receive ethanol in association with: distilled water (10mL/kg); group I, metformin (200mg/kg)+nifedipine (10mg/kg); group II, plant extract (100 and 200mg/kg) group IV and V, respectively for 28 days. At the end of the treatment, hemodynamic parameters were recorded by the direct method. Animals were sacrificed; blood and organs (aorta, heart, liver, and kidneys) were collected for biochemical and histological analysis. Phytochemistry and HPLC-DAD-HRESI-MS were used to determine the major compounds of the extract. The administration of sucrose, alcohol, and STZ resulted in a significant increase in blood glucose, hemodynamic parameters, and body weight loss. A significant decrease in pancreatic islets size, nitrite, GSH, SOD and catalase activity was observed in HDR. There was also a significant increase in serum triglycerides, total cholesterol, creatinine, bilirubin, and transaminases activity in HDR. The aqueous extract of E. senegalensis, as well as the metformin+nifedipine combination, significantly improved all these parameters. HPLC coupled to both diode array and mass spectrometry detectors revealed the presence of 15 compounds and 11 of them were identified. These results suggest that the aqueous extract of E. senegalensis possess antihypertensive, hypoglycemic, hypolipidemic, cardiomodulator and antioxidant properties involved in the improvement of the metabolic disorders found in HDR. This may be due at least in part to the presence of Erysenegalensein (D, O, N, E), Warangalone, senegalensin and 6,8-diprenylgenistein identified in the extract.

Association between the XKR6 rs7819412 SNP and serum lipid levels and the risk of coronary artery disease and ischemic stroke

BackgroundThe present study aimed to expound the association between the XK related 6 gene (XKR6) rs7819412 single nucleotide polymorphism (SNP) and serum lipid profiles and the risk of coronary artery disease (CAD) and ischemic stroke.MethodsThe genetic makeup of the XKR6 rs7819412 SNP in 1783 unrelated participants (controls, 643; CAD, 588 and ischemic stroke, 552) of Han Chinese was obtained by the Snapshot technology.ResultsThe genotypic frequencies of the SNP were disparate between CAD (GG, 81.0%; GA/AA, 19.0%) or ischemic stroke (GG, 81.2%; GA/AA, 18.8%) patients and healthy controls (GG, 85.7%, GA/AA, 14.3%; P < 0.05 vs. CAD or ischemic stroke; respectively). The A allele frequency was also diverse between CAD (10.1%) or ischemic stroke (10.0%) and control groups (7.5%; P < 0.05 vs. CAD or ischemic stroke; respectively). The GA/AA genotypes and A allele were associated with high risk of CAD and ischemic stroke (CAD: P = 0.026 for GA/AA vs. GG, P = 0.024 for A vs. G; Ischemic stroke: P = 0.029 for GA/AA vs. GG, P = 0.036 for A vs. G). The GA/AA genotypes were also associated with increased serum triglyceride (TG) concentration in CAD and total cholesterol (TC) concentration in ischemic stroke patients.ConclusionsThese data revealed that the XKR6 rs7819412 A allele was related to increased serum TG levels in CAD, TC levels in ischemic stroke patients and high risk of CAD and ischemic stroke.

Serum Endocannabinoid Levels in Patients With End-Stage Renal Disease.

ContextPrevious studies have shown that the endocannabinoid system plays a major role in energy metabolism through the actions of its main mediators, 2-arachidonoyl-sn-glycerol (2-AG) and anandamide (AEA).ObjectiveWe examined serum levels of major endocannabinoid mediators and their association with clinical parameters in patients with end-stage renal disease (ESRD).Design and SettingSerum concentrations of 2-AG and AEA were measured in patients on maintenance hemodialysis (MHD) and controls, and correlations with various clinical and laboratory indices were examined. 2-AG was also measured in age and sex-matched healthy subjects for comparison of levels in patients undergoing MHD.Main Outcome MeasureSerum 2-AG.ResultsSerum 2-AG levels were significantly elevated in patients with ESRD compared with healthy controls. Higher levels of 2-AG were found in patients on MHD compared to healthy subjects, and similar findings were seen in a second set of subjects in independent analyses. Among 96 patients on MHD, 2-AG levels correlated significantly and positively with serum triglycerides (ρ = 0.43; P < 0.0001), body mass index (ρ = 0.40; P < 0.0001), and body anthropometric measures and negatively with serum high-density lipoprotein cholesterol (ρ = −0.33; P = 0.001) following adjustment for demographic and clinical variables.ConclusionsIn patients on MHD, levels of serum 2-AG, a major endocannabinoid mediator, were increased. In addition, increasing serum 2-AG levels correlated with increased serum triglycerides and markers of body mass. Future studies will need to evaluate the potential mechanisms responsible for these findings.

238-OR: Long-Term Effects of Intensive Lifestyle Intervention on Cardiovascular Risk Factors in Patients with Diabetes in Real-World Clinical Practice: A 10-Year Longitudinal Study

We previously reported that maintenance of significant weight loss for up to 5 years was attainable in real-world clinical practice among patients with diabetes and obesity and had a positive impact on cardiovascular risk factors. This was predicted by the ability to achieve ≥7% weight loss at 1 year through intensive lifestyle intervention (ILI). In this longitudinal study of the same cohort, we report the 10-year follow-up results. The study included 129 patients with diabetes and obesity enrolled in a 12-week ILI program designed for real-world clinical practice. At 1 year, we divided participants into group A, who maintained &amp;lt;7% weight loss (61 patients, 47.3%), and group B, who maintained ≥7% weight loss (68 patients, 52.7%). We prospectively followed them for 10 years. The total cohort lost on average 10.8±4.6 Kg (-9.7%) at 12 weeks and maintained an average weight loss of 7.7±10 Kg (-6.9%) at 10 years. Group A maintained 4.3±9.5 Kg (-4.3%) and group B maintained 10.8±9.3 Kg (-9.3%) of weight loss at 10 years (P&amp;lt;0.001). In group A, A1C decreased from 7.5±1.3% to 6.7±0.9% at 12 weeks but rebounded to 7.7±1.4% at one year and 8.0±1.9% at 10 years. In group B, A1C decreased from 7.4±1.2% to 6.4±0.9% at 12 weeks and rose to 6.8±1.2% at one year and 7.3±1.5% at 10 years (P&amp;lt;0.05 between groups). Despite weight regain, group A maintained significant improvements in LDL and HDL cholesterol, had no change in BP, but significant worsening of serum triglycerides (TG) at 10 years. Group B maintained similar improvements in lipid profile, had a non-significant increase in serum TG at 10 years, but lower BP for the initial 18 months. In conclusion, significant weight reduction in patients with diabetes can be maintained for up to 10 years in real-world clinical practice. A1C and TG worsened with weight regain, while other lipid improvements were maintained. Sustained weight loss is associated with significantly better A1C at 10 years. Disclosure H. Zhang: None. S. Tomah: Stock/Shareholder; Self; Amarin Corporation. A. Mottalib: None. S. Ashrafzadeh: None. O. Hamdy: Advisory Panel; Self; AstraZeneca, Sanofi-Aventis. Consultant; Self; Abbott, Merck &amp; Co., Inc. Research Support; Self; National Dairy Council. Stock/Shareholder; Self; Healthimation, LLC.

Crocin attenuates metabolic syndrome-induced osteoporosis in rats.

In the current study, anti-osteoporotic activities of crocin were evaluated in a rat model of metabolic syndrome-induced osteoporosis. Metabolic syndrome was confirmed by increased body weight gain, increased fasting blood glucose, hyperinsulinemia, elevated mean arterial blood pressure, and increased serum triglycerides level. Crocin (5 or 10mg/kg) protected against histological and architectural alteration in bone tissues. Further, it ameliorated the decline in the bone formation markers serum alkaline phosphatase activity and osteocalcin level and inhibited the rise in the bone resorption markers serum tartrate-resistant acid phosphatase and collagen cross-linking carboxyterminal telopeptide, type I. Crocin anti-inflammatory properties were confirmed by a significant decline in serum interleukin-6 and tumor necrosis factor-α. Crocin mitigated oxidative stress in femur distal epiphysis tissues. Mechanically, crocin enhanced both the longitudinal and perpendicular forces of femurs. The current data highlight a protective activity that can be attributed, at least partly, to its anti-inflammatory and antioxidant activities. PRACTICAL APPLICATIONS: Metabolic syndrome is a serious health problem. Its prevalence is present in approximately 25% of all adults. Complications of metabolic syndrome include osteoporosis. This poses high risk of fractures and represents a heavy health, social, and economic burden. The current study highlights the antiosteoporotic activities of crocin in an experimental model of osteoporosis. Thus, crocin and/or other structurally related carotenoids can be lead compounds for synthesizing more potent and bioavailable molecules. These are expected to be devoid of the hazardous adverse effects of the currently available medicaments.

Higher dietary acid load potentially increases serum triglyceride and obesity prevalence in adults: An updated systematic review and meta-analysis.

BackgroundIn the current meta-analysis, we aimed to systematically review and summarize the eligible studies evaluating the association between dietary acid load in terms of potential renal acid load (PRAL) and net-endogenous acid production (NEAP) with anthropometric parameters and serum lipids in adult population.MethodsIn a systematic search from PubMed, Scopus, Web of Sciences and Cochrane electronic databases up to December 2018, relevant studies were included. Cross-sectional, case control or cohort studies evaluating the association between PRAL and NEAP with the mean values of body mass index (BMI), waist circumference (WC), low and high density lipoprotein cholesterol (LDL, HDL), triglyceride (TG), total cholesterol (TC) and the prevalence of obesity were included.ResultsAccording to our results, having higher dietary acid load content in terms of high PRAL scores was associated with higher triglyceride concentrations (weighted mean difference (WMD): 3.468; confidence interval (CI): -0.231, 7.166, P = 0.04) and higher obesity prevalence (30% and 27% in highest versus lowest categories). Accordingly, being in the highest category of NEAP was associated with higher prevalence of obesity (25% and 22% in highest versus lowest category). In subgroup analysis, higher PRAL scores was associated with higher BMI in women (WMD: 0.122; CI: -0.001, 0.245; P = 0.049) and higher NEAP in men (WMD: 0.890; CI: 0.430, 1.350; P < 0.001). There was no association between dietary acid load and other studied parameters.ConclusionsIn the current meta-analysis, high dietary acid load content was associated with higher serum triglyceride concentrations and higher obesity prevalence. Reducing dietary acid load content might be a useful preventive strategy against obesity and metabolic disorders.